GeneBe

SEPSECS

protein-coding

Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase

Gene summary

The amino acid selenocysteine is the only amino acid that does not have its own tRNA synthetase. Instead, this amino acid is synthesized on its cognate tRNA in a three step process. The protein encoded by this gene catalyzes the third step in the process, the conversion of O-phosphoseryl-tRNA(Sec) to selenocysteinyl-tRNA(Sec).[provided by RefSeq, Mar 2011]

MANE transcript

NM_016955.4

Inheritance

AR

ClinVar variants

P:123U:152B:183

Top phenotype

Pontocerebellar hypoplasia, type 2D

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr4:25,120,014-25,160,550

External References & Databases

Ensembl (ENSG00000109618)NCBI Gene (51091)OMIM (613009)HGNC:30605GenCCUniProt (Q9HD40)AlphaFoldClinVar (SEPSECS)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~40.5 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pontocerebellar hypoplasia type 2SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016759

Submitter: Orphanet

pontocerebellar hypoplasia type 2DMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0013438

Submitter: Ambry Genetics

pontocerebellar hypoplasia type 2DDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013438

Submitter: Natera

progressive cerebello-cerebral atrophySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016589

Submitter: Orphanet

pontocerebellar hypoplasia type 2DDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013438

Submitter: G2P

pontocerebellar hypoplasia type 2DSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013438

Submitter: PanelApp Australia

pontocerebellar hypoplasia type 2DSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013438

Submitter: Labcorp Genetics (formerly Invitae)

pontocerebellar hypoplasia type 2DDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013438

Submitter: Broad Center for Mendelian Genomics

Clinical Genomic Database (CGD)

Pontocerebellar hypoplasia, type 2DAR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 12920088; 20920667; 25044680Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SEPSECS variants in ClinVar

21 Conditions Cataloged
not providedTotal: 470
Pontocerebellar hypoplasia type 2DTotal: 164
Inborn genetic diseasesTotal: 67
not specifiedTotal: 21
SEPSECS-related disorderTotal: 13
Pontoneocerebellar hypoplasiaTotal: 6
Spinal rigidityTotal: 1
KyphosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016955.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
7
clinvar
179
clinvar
 187
missense
1
clinvar
10
clinvar
142
clinvar
3
clinvar
1
clinvar
 157
nonsense
11
clinvar
21
clinvar
1
clinvar
 33
start loss
1
clinvar
1
clinvar
 2
frameshift
28
clinvar
29
clinvar
 57
splice donor/acceptor (+/-2bp)
20
clinvar
2
clinvar
 22
Total42811521821458

Highest pathogenic variant AF is 0.00008181146

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_016955.4RefSeqNP_058651.311MANE Select
ENST00000382103.7EnsemblENSP00000371535.211MANE Select
NM_001410714.1RefSeqNP_001397643.112Standard
ENST00000358971.7EnsemblENSP00000351857.33Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Selenocompound metabolism - Homo sapiens (human)
  • Aminoacyl-tRNA biosynthesis - Homo sapiens (human)
  • Selenium Metabolism and Selenoproteins
  • Selenocysteine synthesis
  • Metabolism of amino acids and derivatives

Biological Process

  • selenocysteine incorporation
  • selenocysteine metabolic process
  • selenocysteinyl-tRNA(Sec) biosynthetic process

Molecular Function

  • tRNA binding
  • protein binding
  • phosphoseryl-selenocysteinyl-tRNA selenium transferase activity

Cellular Component

  • nucleus
  • cytoplasm
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000382103
Coding exons
11
Length
40578
Individuals with no LoFs
125583
Homozygous LoFs
0
Heterozygous LoFs
165
Defined
125748
p
0.000656
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.02142692700.9960.00001283260
Missense (PolyPhen)94105.420.891711293
Synonymous2.106995.00.7260.00000455972
Loss of Function1.601624.60.6510.00000138295

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000250.00025rare
Latino/Admixed American0.000260.00026rare
Ashkenazi Jewish0.000200.00020rare
East Asian0.0000540.000054rare
Finnish0.00540.0054notable
European (Non-Finnish)0.000230.00023rare
South Asian0.000160.00016rare
Other0.000330.00033rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Converts O-phosphoseryl-tRNA(Sec) to selenocysteinyl- tRNA(Sec) required for selenoprotein biosynthesis. {ECO:0000269|PubMed:17142313}.;

Recessive Scores

pRec
0.156

Intolerance Scores

LoFtool
0.412
RVIS EVS
0
RVIS percentile EVS
53.73

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
N
Indispensability score
0.209

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.